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Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes

Lysosomes possess a multitude of biological functions and are known to play a crucial role in the proliferation and metastasis of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically investigate the potential role of lysosomes-related genes (LRGs) in the development of he...

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Autores principales: Zhang, Aichun, Jin, Yangzi, Zou, Xinbo, Zhang, Shuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344503/
https://www.ncbi.nlm.nih.gov/pubmed/37443469
http://dx.doi.org/10.1097/MD.0000000000034275
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author Zhang, Aichun
Jin, Yangzi
Zou, Xinbo
Zhang, Shuo
author_facet Zhang, Aichun
Jin, Yangzi
Zou, Xinbo
Zhang, Shuo
author_sort Zhang, Aichun
collection PubMed
description Lysosomes possess a multitude of biological functions and are known to play a crucial role in the proliferation and metastasis of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically investigate the potential role of lysosomes-related genes (LRGs) in the development of heterogeneity and prognosis in HNSCC. Publicly available transcriptome and clinical data of HNSCC were obtained and analyzed using consensus clustering to identify molecular subtypes. A risk model based on LRGs was developed and evaluated, including its correlation with clinical features, immune infiltration, drug sensitivity, and response to immune therapy. Gene set enrichment analysis was conducted to explore relevant pathways, and a prognostic nomogram model for HNSCC was constructed and evaluated. In this study, we identified 542 LRGs that exhibited differential expression in HNSCC, with 116 of these being significantly associated with overall survival. Two LRGs-derived molecular subtypes were identified, which displayed significant differences in prognosis and immune cell infiltration. Additionally, a prognostic risk model was developed, which included 13 LRGs. This model successfully divided HNSCC into low-risk and high-risk groups with different prognoses and immune cell infiltrations. The LRGs-derived risk signature was associated with immune infiltration, clinical features, drug sensitivity and immunotherapy response. The good prognosis of the low-risk group was linked to the activation of immune response-related processes and the inhibition of pathways such as necroptosis and neutrophil extracellular trap formation. Patients in the low-risk group had better immune therapy response, while those in the high-risk group had higher drug sensitivity. Finally, our nomogram, which combines clinical N staging and LRG-derived model, demonstrated excellent prognostic evaluation performance as shown by decision curve analysis and calibration curve. The study provides a comprehensive analysis of the expression and prognostic significance of LRGs in HNSCC, leading to the identification of 2 distinct molecular subtypes and the development of a risk model based on LRGs.
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spelling pubmed-103445032023-07-14 Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes Zhang, Aichun Jin, Yangzi Zou, Xinbo Zhang, Shuo Medicine (Baltimore) 5700 Lysosomes possess a multitude of biological functions and are known to play a crucial role in the proliferation and metastasis of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically investigate the potential role of lysosomes-related genes (LRGs) in the development of heterogeneity and prognosis in HNSCC. Publicly available transcriptome and clinical data of HNSCC were obtained and analyzed using consensus clustering to identify molecular subtypes. A risk model based on LRGs was developed and evaluated, including its correlation with clinical features, immune infiltration, drug sensitivity, and response to immune therapy. Gene set enrichment analysis was conducted to explore relevant pathways, and a prognostic nomogram model for HNSCC was constructed and evaluated. In this study, we identified 542 LRGs that exhibited differential expression in HNSCC, with 116 of these being significantly associated with overall survival. Two LRGs-derived molecular subtypes were identified, which displayed significant differences in prognosis and immune cell infiltration. Additionally, a prognostic risk model was developed, which included 13 LRGs. This model successfully divided HNSCC into low-risk and high-risk groups with different prognoses and immune cell infiltrations. The LRGs-derived risk signature was associated with immune infiltration, clinical features, drug sensitivity and immunotherapy response. The good prognosis of the low-risk group was linked to the activation of immune response-related processes and the inhibition of pathways such as necroptosis and neutrophil extracellular trap formation. Patients in the low-risk group had better immune therapy response, while those in the high-risk group had higher drug sensitivity. Finally, our nomogram, which combines clinical N staging and LRG-derived model, demonstrated excellent prognostic evaluation performance as shown by decision curve analysis and calibration curve. The study provides a comprehensive analysis of the expression and prognostic significance of LRGs in HNSCC, leading to the identification of 2 distinct molecular subtypes and the development of a risk model based on LRGs. Lippincott Williams & Wilkins 2023-07-14 /pmc/articles/PMC10344503/ /pubmed/37443469 http://dx.doi.org/10.1097/MD.0000000000034275 Text en Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle 5700
Zhang, Aichun
Jin, Yangzi
Zou, Xinbo
Zhang, Shuo
Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes
title Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes
title_full Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes
title_fullStr Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes
title_full_unstemmed Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes
title_short Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes
title_sort molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes
topic 5700
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344503/
https://www.ncbi.nlm.nih.gov/pubmed/37443469
http://dx.doi.org/10.1097/MD.0000000000034275
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